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Expanding human population and economic growth have led to large-scale conversion of natural habitat to human-dominated landscapes with consequent large-scale declines in biodiversity. Conserving biodiversity, while at the same time meeting expanding human needs, is an issue of utmost importance. In this paper we develop a spatially explicit landscape-level model for analyzing the biological and economic consequences of alternative land-use patterns. The spatially explicit biological model incorporates habitat preferences, area requirements and dispersal ability between habitat patches for terrestrial vertebrate species to predict the likely number of species that will be sustained on the landscape. The spatially explicit economic model incorporates site characteristics and location to predict economic returns for a variety of potential land uses. We apply the model to search for efficient land-use patterns that maximize biodiversity conservation objectives for given levels of economic returns, and vice versa. We apply the model to the Willamette Basin, Oregon, USA. By thinking carefully about the arrangement of activities, we find land-use patterns that sustain high levels of biodiversity and economic returns. Compared to the 1990 land-use pattern, we show that both biodiversity conservation and the value of economic activity could be increased substantially.